Human neurological disorders are among the most challenging areas of translational research. The difficulty of acquiring human neural samples or specific representative animal models has necessitated a multifaceted approach to understanding disease pathology and drug discovery. The dedifferentiation of somatic cells to human induced pluripotent stem cells (hiPSCs) for the generation of neural derivatives has broadened the capability of biomedical research to study human cell types in neurological disorders. The initial zeal for the potential of hiPSCs for immediate biomedical breakthroughs has evolved to more reasonable expectations. Over the past decade, hiPSC technology has demonstrated the capacity to successfully establish “disease in a dish” models of complex neurological disorders and to identify possible novel therapeutics. However, as hiPSCs are used more broadly, an increased understanding of the limitations of hiPSC studies is becoming more evident. In this study, we review the challenges of studying neurological disorders, the current limitations of stem cell-based disease modeling, and the degrees to which hiPSC studies to date have demonstrated the capacity to fill essential gaps in neurological research.

中文翻译：

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干细胞的进化、疾病建模和神经系统疾病的药物发现。

人类神经系统疾病是转化研究中最具挑战性的领域之一。获取人类神经样本或特定代表性动物模型的困难使得需要采用多方面的方法来了解疾病病理学和药物发现。将体细胞去分化为人类诱导多能干细胞 (hiPSC) 以产生神经衍生物，这拓宽了生物医学研究在神经系统疾病中研究人类细胞类型的能力。对 hiPSC 立即实现生物医学突破的潜力的最初热情已经演变为更合理的预期。在过去的十年中，hiPSC 技术已经证明能够成功建立复杂神经系统疾病的“盘中疾病”模型并确定可能的新疗法。然而，随着 hiPSC 的应用越来越广泛，对 hiPSC 研究局限性的理解越来越明显。在这项研究中，我们回顾了研究神经系统疾病的挑战、基于干细胞的疾病建模的当前局限性，以及迄今为止 hiPSC 研究在多大程度上证明了填补神经学研究中基本空白的能力。